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At least 811 records · Page 45Linked to original sources
PubMed1998

[Clinical activity spectrum of irinotecan].

Irinotecan (CPT11), a topoisomerase I inhibitor, is a new cytotoxic agent with a broad spectrum of clinical activity. Two main schedules have been studied and produce similar activity and side-effects: the "european" one--350 mg/m2 every 21 days-, and the "japanese-north american" one where CPT11 is given at a weekly dose of 100-120 mg/m2 for 4 consecutive weeks followed by a 2 week rest period. Activity was initially characterized in advanced colorectal cancers; response rates, disease free-survival and overall survival were 11%, 7-10 months and 8-11 months in patients failing fluoropyrimidine based chemotherapy--statistically improved as compared to best supportive care and infusional fluorouracil-, and 20-30% in patients not previously treated. An interesting activity with response rates of 20-22% (increased to 65% in combination with CDDP) has been shown in relapsed cervix carcinomas; in gastric carcinomas response rates of 20% have been shown, reaching 48% in combination with CDDP. Response rates of 20-22%, increased to 40-60% when irinotecan was associated to CDDP have been reported in non small cell lung cancer and esophagal carcinomas. Further studies are needed for other GI tract cancers, ovarian and head and neck carcinomas while minimal or no clinically meaningful activity has been reported in advanced breast cancer, and haematological malignancies. Irinotecan can be combined to fluoropyrimidines, raltitrexed, cisplatin, carboplatin and oxaliplatin, to gemcitabine, etoposide, vinorelbine and taxanes with flexible schedules (weekly, every 2 weeks, every 21 days. Most of these combinations have an additive or supra additive activity. Its mechanism of action, the spectrum of activity and the acceptable risk-benefit ratio point to irinorecan as a major advance in the field of cytotoxic anticancer therapy.

Adenocarcinoma↗
PubMed1995

Trends in survival of childhood malignancy for the past three decades. I: Leukemia, malignant lymphoma, neuroblastoma, retinoblastoma and neoplasms of the urinary and digestive organs. The Committee for the Studies of the Treatments and the Biological Characteristics of Childhood Cancers.

Survival of some types of childhood neoplasms has improved considerably but remained poor for other types. Improvement in survival rate of common types of childhood neoplasms over the past three decades was assessed at the largest children's hospital in Japan. Using the data of the cancer registry of the hospital which recorded all the patients from 1965 to 1993, totalling 1026 cases, survival rate was analyzed for each type of neoplasm categorized by the S-classification for childhood neoplasms, a modification of the International Classification of Diseases. Survival was assessed for five 5 year periods from 1965 and a 4 year period from 1990-93. The 5 year survival rate for all neoplasms combined improved from 21.8% in the 1965-69 period to 73.3% in the 1985-89 period. Female patients' survival was better than male patients' in all periods. The improvement in survival rate was considerable for leukemia and malignant lymphoma, fairly good for neoplasms of the renal (mostly Wilms' tumor) and digestive (mostly hepatoblastoma) organs and moderate for neuroblastoma. Overall, survival rates of childhood neoplasms improved considerably. Much of this improvement was explained by a great improvement in survival rates of neoplasms of the blood which constituted the majority of patients.

Child↗
PubMed2000

Technetium-99m labelled macroaggregated albumin arterial catheter perfusion scintigraphy: prediction of gastrointestinal toxicity in hepatic arterial chemotherapy.

Gastrointestinal toxicity from hepatic arterial infusion (HAI) of floxuridine in patients with liver metastases is probably due to extrahepatic perfusion or to partial escape of the drug from first-pass liver extraction. The aim of this study was to verify the role of technetium-99m-labelled macroaggregated albumin (99mTc-MAA) arterial catheter perfusion scintigraphy at the beginning of each chemotherapy cycle in decreasing or preventing gastrointestinal toxicity. We studied 167 consecutive patients. On the basis of the scintigraphic follow-up and the presence or absence of an intrahepatic arteriovenous shunt (IHAVS), we classified our patients into the following groups: (1) FU+ hepatic distribution pattern (DP), comprising 29 patients with regular scintigraphic follow-up who showed the expected distribution pattern at each control or a distribution pattern with transient alterations (extrahepatic escape) promptly reversed by the replacement of the catheter. Among these 29 patients there was one case of gastrointestinal toxicity. (2) FU- hepatic DP, comprising 128 patients who were evaluated with 99mTc-MAA only at the beginning of the first chemotherapy cycle, showed the expected distribution pattern and underwent HAI with no further scintigraphic evaluation. Among these 128 patients there were 28 cases of gastrointestinal toxicity. (3) FU+ pulmonary DP, comprising three patients with abnormally elevated pulmonary uptake (higher than 5%) and with regular scintigraphic follow-up. There were two cases of gastrointestinal toxicity among these three patients. (4) FU- pulmonary DP, comprising seven patients with abnormally elevated pulmonary uptake and without regular scintigraphic follow-up. There were four cases of gastrointestinal toxicity among these seven patients. The incidence of toxicity was significantly higher in group FU- hepatic DP than in group FU+ hepatic DP (21.9% vs 3.4%, P<0.05). In both the FU+ pulmonary DP and FU- pulmonary DP groups, the incidence of gastrointestinal toxicity was higher than 50%, with no significant difference between them. We conclude that, when performing 99mTc-MAA perfusion scintigraphy, the presence of an abnormally elevated pulmonary uptake (IHAVS higher than 5%) is the most relevant positive prognostic index for the development of gastrointestinal toxicity. Furthermore, in the absence of abnormal pulmonary uptake (IHAVS lower than 5%), strict scintigraphic follow-up is useful since it is able to promptly diagnose the presence of extrahepatic abdominal perfusion and thus to prevent the occurrence of gastrointestinal toxicity.

Adult↗
PubMed2001

Changes in T cell subsets, interleukin-6 and C-reactive protein after laparoscopic and open colorectal resection for malignancy.

BACKGROUND: Attenuation of the immune response to surgery, as demonstrated with the laparoscopic approach to cholecystectomy, has potential benefits in patients undergoing laparoscopic colonic resection for malignancy. We aimed to study the perioperative immune response in patients undergoing laparoscopically assisted and open surgery for colorectal cancer. METHODS: This study involved 23 patients undergoing laparoscopically assisted (n = 13) and open surgery (n = 10). Interleukin-6 (IL-6) C-reactive protein (CRP), the total lymphocyte count, and the CD3, CD4, CD8, CD16, and CD19 lymphocyte subpopulations were assayed preoperatively and at 4, 8, 10, 24, 48, and 168 h postoperatively. RESULTS: Significant rises in IL-6 and CRP were demonstrated within 4 and 24 h, respectively (p < 0.001) in both groups. However, no significant difference between the groups was seen. Significant decreases in total lymphocyte count and all T cell subsets were demonstrated in both groups, beginning at 4 h (p < 0.01). However, no significant difference between the groups was seen. All parameters, excluding CRP, had returned to baseline by 7 days postoperatively in both groups. CONCLUSIONS: Patients with malignancy exhibit significant perioperative immune disturbance with laparoscopically assisted and open surgery. The current data do not provide justification for the laparoscopically assisted approach on grounds of immune preservation.

Aged↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced breast cancer: a phase II trial of the EORTC breast cancer cooperative group.

Twenty-nine evaluable patients with extensively pretreated breast cancer received PALA, a new pyrimidine antimetabolite. The drug was given by intravenous infusion over 60 min, at a daily dose of 2.5 g/m2 for 2 consecutive days. Courses were repeated at 2-week intervals and doses were escalated to toxicity. Two objective partial remissions were observed, lasting for 3 and 4.5 months respectively. Toxic effects were dose-related and consisted mainly of mucocutaneous manifestations, i.e., skin rashes, stomatitis, diarrhea, conjunctivitis and corneal ulcerations. Evidence of antitumor potential in far-advanced disease and lack of myelosuppression point to the need for additional trials of PALA in a more favorable selection of patients with breast cancer.

Adult↗
PubMed2006

Less vigorous surgery for second primary lung cancer.

BACKGROUND: Patients with second primary lung cancer (SPLC) have a heterogeneous background. The optimum modality of treatment for SPLC patients has not yet been determined. The objective of this study was to attempt to identify the value of less vigorous therapies such as segmentectomy or video-assisted thoracic surgery (VATS) in SPLC. METHODS: We retrospectively reviewed the medical records of 46 patients who underwent resection for SPLC in Fukuoka University Hospital between January 1994 and April 2005. Patients were separated into two groups (LVT: less vigorous therapy including segmentectomy or VATS lobectomy; LCT: lobectomy with conventional thoracotomy). The characteristics of each group were evaluated and survival rates were analyzed at 5 years after surgery. RESULTS: The mean amount of blood loss was found to be significantly different ( P = 0.0062) with 59.44 +/- 14.00 ml for LVT cases and 254.48 +/- 63.62 ml for LCT. None of the LVT patients experienced postoperative complications. The 5-year survival rate was 62.7 % for LVT and 57.7 % for LCT. There was no significant difference in survival rates between these groups. CONCLUSIONS: Although differences were seen in the characteristics, less invasive surgery such as VATS or segmentectomy may be a feasible treatment for SPLC.

Aged↗
PubMed1984

Localization and alteration of mono-, di-, and trifucosyl alpha 1----3 type 2 chain structures during human embryogenesis and in human cancer.

Distribution patterns of specific fucose-containing antigens having X determinant (Gal beta 1----4[Fuc alpha 1----3]GlcNAc) as well as the di- or trimeric X determinants (Gal beta 1----4[Fuc alpha 1----3]GlcNAc beta 1----3Gal beta 1----4[Fuc alpha 1----3]-GlcNAc) in the developing human embryo and fetus and in human cancer have been examined using immunohistological techniques. Tissue sections were stained with monoclonal antibody FH3, which defines X determinant, and with monoclonal antibody FH4, which defines di- or trimeric X determinant. The following general trends in the expression of the antigens defined by FH3 and FH4 have been observed: (a) A well-organized, orderly appearance and disappearance of the antigens was observed during the histogenesis of various epithelia of gastrointestinal and other organs. The developmental stage exhibiting the maximum antigen expression is different for each organ. (b) The X determinant defined by FH3 was expressed approximately 2 wk earlier than the di- or trimeric X determinant defined by FH4, and the antigen defined by FH4 regressed more rapidly and more completely than the X determinant defined by FH3 on further development of epithelial tissue. Thus, expression of the FH4 antigen is highly limited to specific types of cells in newborn and adult epithelial tissues. (c) The antigen defined by FH4 was strongly expressed in the majority of tubular and papillary adenocarcinoma of stomach, adenocarcinoma of colon, and infiltrating ductal carcinoma of breast and its metastatic lesions. No antigen was found in poorly differentiated stomach adenocarcinoma, squamous lung carcinoma, and many other types of tumors from ovary, testis, prostate, skin, and muscle. The presence of the antigen defined by FH4 is therefore limited to carcinoma of the stomach, colon, and breast and can be regarded as a retrograde expression of the antigen to a certain stage of fetal development in which expression of this antigen was maximal.

Adult↗
PubMedDate not supplied

SPan-1 and exocrine pancreatic carcinoma. The clinical role of a new tumor marker.

AIMS OF THE STUDY: Considerable progress has been made in imaging techniques over the past few years, yet this has not resulted in the ability to reach an earlier diagnosis of exocrine pancreatic cancer. The search for a noninvasive diagnostic tool capable of early diagnosis has led to the development of a series of serum tumor markers. This article discusses the clinical evaluation of SPan-1 and its comparison with established markers such as CA 19.9, CEA, TPA and CA 242. METHODS: The markers were measured in preoperative serum samples collected from 46 patients who had undergone surgery for ductal carcinoma of the pancreas, 20 patients with chronic pancreatitis, and 23 patients with other digestive neoplasms. RESULTS: The sensitivity, specificity and diagnostic accuracy for pancreatic cancer were as follows: [table: see text] CONCLUSIONS: The antigenic determinant SPan-1, recognized by monoclonal antibodies, is elevated in sera of patients with exocrine pancreatic cancer. SPan-1 may be considered as an additional useful and reliable serum marker for the detection of this neoplasm, but it does not significantly improve the diagnostic accuracy obtained with CA 19.9.

Adult↗
PubMed2000

The use of a rapid ELISPOT assay to analyze peptide-specific immune responses in carcinoma patients to peptide vs. recombinant poxvirus vaccines.

An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon gamma production has been used to analyze specific T cell responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA). Assays were performed on peripheral blood mononuclear cells (PBMC) of HLA-A2-positive patients with CEA-expressing carcinomas, both before and after vaccination with CEA-based vaccines, and from HLA-A2-positive healthy blood donors. The ELISPOT assay utilized aliquots of frozen PBMC, and assays were performed after 24 h in culture with peptide to rule out any artifacts due to long-term in vitro stimulation cycles. An internal standard was used for each assay to define reproducibility of the assay, and all samples from a given patient (pre- and post-vaccination, with both the Flu and CEA peptides) were analyzed simultaneously. The results indicated a trend towards healthy blood donors having higher levels of Flu-specific T cell precursors than do colon carcinoma patients, but these results were not statistically significant (P = 0.06). On the other hand, slightly higher CEA-specific T cell responses were observed in cancer patients with CEA-expressing carcinomas than in healthy blood donors. PBMC from two CEA-based vaccine clinical trials were analyzed for T cell responses to the same CEA peptide and to the Flu control peptide. The first trial consisted of three monthly vaccinations of CEA peptide (designated PPP) in adjuvant. The second trial consisted of cohorts receiving three monthly vaccinations of avipox-CEA recombinant (designated AAA) or cohorts receiving a primary vaccination with recombinant vaccinia-CEA followed by two monthly vaccinations with avipox-CEA (designated VAA). Few, if any, CEA-specific T cell responses were seen in the PPP vaccinations, while the majority of patients receiving the poxvirus CEA recombinants demonstrated increases in CEA-specific T cell responses and no increases in Flu-specific responses. CEA-specific IgG responses were also demonstrated in patients following recombinant CEA poxvirus vaccinations. Statistical analyses of the T cell responses to the same CEA peptide demonstrated a P value of 0.028 for the recombinant poxvirus vaccines, as compared with the peptide vaccine. There were no differences seen (P = 0.37) in Flu-specific responses after these two types of CEA vaccination. These results thus provide the first evidence that poxvirus recombinant-based vaccines are more potent in the initiation of tumor-antigen-specific T cell responses than vaccines employing peptide in adjuvant, when assays are conducted in an identical manner, and in defining responses to the same peptide. These results also demonstrate for the first time that an ELISPOT assay, performed over a 24-h period and without in vitro sensitization, can be successfully used to monitor immune responses to a tumor-associated antigen in cancer patients.

Adjuvants, Immunologic↗
PubMed2002

One-stage surgical management of concomitant abdominal aortic aneurysm and gastric or colorectal cancer.

One-stage surgical management of concomitant abdominal aortic aneurysm (AAA) and gastric or colorectal cancer should provide certain benefits. We reviewed the records of 21 patients with both AAA and gastric or colorectal cancer who underwent one-stage surgical management. Four had distal gastrectomy, 2 had total gastrectomy, and 5 had abdominoperineal rectal resection transperitoneally; 3 had total gastrectomy transperitoneally and AAA repair extraperitoneally. Two underwent right hemicolectomy and thromboexclusion of the AAA. Two had creation of a temporary ileostomy and implantation of an interposition graft. Two underwent left hemicolectomy, creation of a temporary transversostomy, and implantation of an interposition graft. One had a Hartmann's procedure and implantation of a bifurcated prosthetic interposition graft for AAA. There were no operative deaths or serious postoperative complications. One patient had colorectal ischemia that resolved with conservative treatment. Eighteen of the 21 patients (85.7%) were alive 10 months to 14 years postoperatively. In conclusion, one-stage surgical treatment of concomitant AAA and gastric or colorectal cancer is well tolerated and can avoid the time, financial costs, and patient anxiety involved in a second operation.

Aged↗
PubMed1994

Gut hormones, growth and malignancy.

There is now clear-cut evidence that polypeptide growth factors control the proliferation of the normal gastrointestinal mucosa. Epidermal growth factor (EGF) stimulates normal growth throughout the gastrointestinal tract, and accelerates the healing of ulcerated epithelium. While the effects of gastrin were at first thought to be similarly widespread, the gastrin target now appears to be restricted to the enterochromaffin-like cells in the stomach. Isolated reports suggest that several other hormones, including fibroblast growth factor and the insulin-like growth factors, have similar proliferative effects. In contrast, indirect evidence suggests that somatostatin and transforming growth factor-beta inhibit the growth of the gastrointestinal mucosa. The same growth factors profoundly affect the growth of some gastrointestinal carcinomas. Prolonged hypergastrinaemia increases the risk of development of gastric endocrine tumours, but has no effect on the incidence of gastric adenocarcinoma. Gastrin also stimulates the in vivo growth of 50% of gastric and colorectal carcinoma xenografts, but has no consistent effect on the growth of carcinoma cell lines in vitro. EGF, on the other hand, significantly stimulates proliferation of many gastrointestinal cell lines in culture. Interest has recently focused on autocrine stimulation of gastrointestinal carcinoma growth. Elevated levels of EGF receptor, and of EGF or related mRNAs, have been demonstrated in gastric carcinomas, and the growth of some gastrointestinal cell lines is inhibited by antibodies against EGF, and by antisense oligonucleotides based on EGF mRNA. Similarly gastrin/cholecystokinin antagonists inhibit the growth of several colon carcinoma cell lines, although the spectrum of antagonist potencies suggests that classical gastrin and cholecystokinin receptors are not necessarily involved. Continued research on antagonists may therefore lead to novel therapies for gastrointestinal cancers.

Adult↗